Nasal Inflammation Following Endotoxin Challenge in Patients With Asthma

NCT06270576 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: HS3131
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

A phase I clinical research study aimed at determining mechanisms that regulate airway mucosal inflammation in asthma endotypes using intranasal administration of endotoxin (lipopolysaccharide from E. coli) in healthy controls and subjects diagnosed with asthma.

Conditions

Asthma; Eosinophilic; Asthma

Outcome Measures

Primary Outcomes (1)

• Neutrophil heterogeneity using single cell RNA sequencing

  Neutrophil subset composition as determined by single cell RNAseq is compared to endotype groups using a multivariate linear regression framework for compositional data, employing the additive log ratio transformation. Models will include indicator variables for whether a sample is T1 high, T2 high, T17 high or non-asthmatic and will control for age, sex, and smoking status. AM subset gene expression matrices from scRNAseq will be compared between endotypes using the pseudo bulk approach to account for clustering of cells within subjects. To identify global gene expression programs underlying each endotype, bulk RNAseq gene expression data will be normalized using DESeq2's variance stabilizing transformation and similarly compared between endotypes using linear regression models. A Benjamini-Hochberg adjustment will be used to control the false discovery rate.

  We anticipate that the study will run over 5 years

Study Arms (2)

Asthma Group

ACTIVE COMPARATOR

Subjects diagnosed with one of the three asthma endotypes being studied (T2, T1, or T17).

Drug: Lipopolysaccharides

Control Group

ACTIVE COMPARATOR

Subjects with no diagnosis of asthma or other respiratory disease and are deemed healthy.

Drug: Lipopolysaccharides

Interventions

Lipopolysaccharides DRUG

LPS aka endotoxin is a component of bacterial cell walls and is ubiquitous in the environment. It is found in pet dander, house dust and environmental dusts and has been heavily studied in asthma.

Also known as: Endotoxin, LPS, Clinical reference center lipopolysaccharide, LPS E. Coli O:113

Asthma Group; Control Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants will have asthma diagnosed by a health care provider. Healthy controls are individuals without asthma.
• Written informed consent

You may not qualify if:

• Current or recent illness (in the past 4 weeks)
• Recent asthma exacerbation (past 4 weeks)
• History of nasal perforation or nasal surgery
• Nasal polyposis
• Presence or prior history of cardiac or systemic disease
• Bleeding disorder, use of systemic anticoagulants, or antiplatelet therapy
• Immunocompromised state (HIV, immunoglobulin deficiency, systemic immunosuppressants excluding corticosteroids)
• Use of tobacco or marijuana in the past 2 months or greater than a 10 pack-year smoking history
• Currently pregnant or breastfeeding

Sponsors & Collaborators

• National Jewish Health: lead

Study Sites (1)

National Jewish Health

Denver, Colorado, 80206, United States

Location

MeSH Terms

Conditions

Pulmonary Eosinophilia; Asthma

Interventions

Lipopolysaccharides; Endotoxins

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypereosinophilic Syndrome; Eosinophilia; Leukocyte Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Glycoconjugates; Carbohydrates; Polysaccharides, Bacterial; Polysaccharides; Lipids; Antigens, Bacterial; Antigens; Biological Factors; Bacterial Toxins; Toxins, Biological

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Section Head of Critical Care, Professor of Medicine, Principle Investigator

Study Record Dates

• First Submitted: January 30, 2024
• First Posted: February 21, 2024
• Study Start: April 1, 2024
• Primary Completion (Estimated): April 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: February 21, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)